Q5 LONG ANSWER 10M ★ High-yield

Describe the hormonal agents, targeted therapy and immunotherapy used in cancer.

Pharmacology · 2nd Professional — Para-Clinical

Hormonal Agents in Cancer

Cancer	Approach	Drugs
Breast (oestrogen receptor positive)	Block or deprive of oestrogen	Tamoxifen (a SERM — antagonist in breast, agonist in endometrium and bone, hence endometrial cancer risk and thromboembolism); aromatase inhibitors (letrozole, anastrozole) in postmenopausal women, causing arthralgia and bone loss; fulvestrant (a pure receptor degrader)
Prostate	Androgen deprivation	GnRH agonists (leuprorelide, goserelin) — continuous exposure down-regulates the receptor, causing chemical castration, with a transient flare that must be covered by an antiandrogen; degarelix (antagonist, no flare); bicalutamide, enzalutamide; abiraterone (blocks CYP17 androgen synthesis, given with prednisolone)
Endometrial, renal	Progestogens	Medroxyprogesterone, megestrol
Lymphoma, leukaemia, myeloma	Lymphocytolytic action	Prednisolone, dexamethasone — part of almost every regimen
Thyroid	Suppress TSH drive	Levothyroxine after thyroidectomy

Targeted Therapy

Target	Drugs	Cancer and key toxicity
BCR-ABL tyrosine kinase	Imatinib, dasatinib, nilotinib	Chronic myeloid leukaemia — imatinib converted a fatal disease into a chronic one taken as a daily tablet, and is the model for targeted therapy. Causes oedema, cramps, rash and myelosuppression
HER2	Trastuzumab, pertuzumab, trastuzumab-emtansine	HER2-positive breast and gastric cancer; causes cardiotoxicity, worse with anthracyclines, so cardiac function must be monitored
EGFR	Gefitinib, erlotinib, osimertinib; cetuximab	Non-small cell lung cancer with EGFR mutation; colorectal cancer. Cause an acneiform rash (which correlates with response) and diarrhoea
VEGF (angiogenesis)	Bevacizumab; sunitinib, sorafenib	Colorectal, renal, lung cancer. Cause hypertension, proteinuria, bleeding, impaired wound healing and bowel perforation — surgery must be separated in time
CD20	Rituximab	B-cell lymphoma; also autoimmune disease. Infusion reactions; hepatitis B reactivation, so screening is mandatory
ALK, BRAF, PARP, CDK4/6	Crizotinib; vemurabenib and dabrafenib; olaparib; palbociclib	Lung, melanoma, BRCA-mutated ovarian and breast, hormone-receptor-positive breast cancer
Proteasome	Bortezomib	Multiple myeloma; peripheral neuropathy

CLINICAL PEARL

Targeted therapy only works if the target is present, which is why the diagnostic test and the drug are inseparable. Trastuzumab is useless and merely toxic in HER2-negative disease; an EGFR inhibitor does little without the mutation. This has changed how cancer is classified — by molecular alteration as much as by organ of origin — and it means the pathology laboratory determines the prescription.

Immunotherapy

Checkpoint inhibitors — tumours evade immune attack by engaging inhibitory checkpoints on T cells. PD-1 inhibitors (nivolumab, pembrolizumab), PD-L1 inhibitors (atezolizumab) and CTLA-4 inhibitors (ipilimumab) release that brake
Used in melanoma, non-small cell lung cancer, renal, bladder and head and neck cancer, with durable responses in a minority that were previously unattainable
Immune-related adverse events — the price of removing the brake is autoimmunity affecting any organ: colitis, hepatitis, pneumonitis, thyroiditis, hypophysitis, adrenal insufficiency, nephritis, dermatitis, myocarditis
These are treated with corticosteroids, and with additional immunosuppression if severe — the opposite of how conventional chemotherapy toxicity is managed, and a distinction that must be recognised early
Car-T cell therapy — the patient's T cells are engineered to express a chimeric receptor against a tumour antigen (CD19 in B-cell malignancy); causes cytokine release syndrome (treated with tocilizumab, an IL-6 receptor blocker) and neurotoxicity
Other approaches — interferon-alpha, interleukin-2, BCG instillation for superficial bladder cancer, and therapeutic monoclonal antibodies

Supportive Therapy in Oncology

Antiemetics — 5-HT3 antagonists with dexamethasone and an NK1 antagonist for highly emetogenic regimens
Growth factors — G-CSF (filgrastim) to shorten neutropenia and permit dose intensity; erythropoietin for chemotherapy-induced anaemia, used cautiously as it may promote tumour growth and thrombosis
Prevention of tumour lysis syndrome — hydration with allopurinol or rasburicase in bulky, rapidly proliferating tumours
Bisphosphonates or denosumab for bone metastases and hypercalcaemia of malignancy
Analgesia by the WHO ladder, given by the clock with breakthrough doses; opioids are under-used in India and their proper use is a core part of cancer care
Prophylaxis — antimicrobial and antifungal prophylaxis in prolonged neutropenia, and mouth care for mucositis

Comparison of Cytotoxic and Targeted Therapy

Feature	Cytotoxic chemotherapy	Targeted therapy
Basis of selectivity	Rate of proliferation — a property normal tissues share	A specific molecular alteration present in the tumour and absent in normal cells
Patient selection	By tumour type and stage	By molecular testing — the drug is useless without the target, so the test and the drug are inseparable
Typical toxicity	Myelosuppression, mucositis, alopecia, nausea — the rapidly dividing normal tissues	Reflects the target’s normal function — rash with EGFR inhibitors, hypertension with VEGF inhibitors, cardiotoxicity with trastuzumab
Route and duration	Usually intravenous, in cycles with recovery periods	Often oral and continuous, for months or years
Resistance	Efflux pumps, repair, altered target	Secondary mutation at the target — hence successive generations of inhibitor, as with osimertinib for the EGFR T790M mutation
Cost	Low, largely generic	Very high, though generics and biosimilars have transformed access in India

Applied Aspects

Recognise immune-related adverse events early — diarrhoea in a patient on a checkpoint inhibitor is autoimmune colitis until proved otherwise, and treating it as infective delays the steroids that are needed
Screen for hepatitis B before rituximab and for tuberculosis before any prolonged immunosuppression
Test before prescribing a targeted agent; giving one without the molecular target wastes money that most Indian patients cannot afford and exposes them to toxicity for no benefit
Stop antiangiogenic agents well before surgery and do not restart until wounds have healed
Imatinib and its successors are available as generics in India at a small fraction of the original price, and the resulting access has been a genuine public health achievement
Palliative care is not the failure of oncology but part of it, and early integration improves both quality of life and, in some studies, survival
Tamoxifen requires vigilance for endometrial change — any postmenopausal bleeding must be investigated, since it is an agonist at that receptor
Aromatase inhibitors cause bone loss and arthralgia, so bone density should be assessed and calcium, vitamin D and sometimes a bisphosphonate given
Cover the GnRH agonist "flare" with an antiandrogen in prostate cancer with spinal metastases, or cord compression may result
Checkpoint inhibitor toxicity can appear months after the last dose, and any clinician seeing the patient must know they have received one
Do not treat immune colitis with antimotility drugs; steroids are the treatment, and delay risks perforation
Trastuzumab cardiotoxicity is usually reversible, unlike that of anthracyclines, and often allows rechallenge after recovery — a practical difference worth knowing
Endocrine therapy is taken for 5 to 10 years in breast cancer, and adherence falls steadily with time; asking about side effects and addressing them is what keeps patients on treatment
Molecular testing must precede the prescription, and where it is unaffordable the drug should not simply be given on the assumption that the target is present
Adherence to an oral targeted agent cannot be assumed merely because it is a tablet; missed doses in chronic myeloid leukaemia are strongly associated with loss of molecular response
BCG instillation for superficial bladder cancer is an old and highly effective immunotherapy, and a reminder that stimulating a local immune response predates the checkpoint inhibitors by decades

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